This Journal of the American College of Cardiology state-of-the-art review of Brugada syndrome conveys a comprehensive update and overall perspective on this rare but significant cause of sudden cardiac death. The following are key points to remember:

1. Brugada syndrome is a rare genetic entity thought responsible for 4-12% of all suddden deaths and is characterized by typical electrocardiographic (ECG) findings leading to ventricular fibrillation and sudden cardiac death (SCD). ECG findings may occur spontaneously or after provocative drug testing.
2. Prevalence ranges from 1 in 5,000 to 1 in 2,000 and is 8-10 times more common in men than women.
3. Symptoms include syncope, seizures, nocturnal agonal breathing, or SCD. Lethal arrhythmias often occur during rest or sleep but may occur with fever. Symptoms occur most often in adulthood with apparent influence from sex-related hormones.
4. Resting ECG may show type 1 (“coved type”) pattern, which is diagnostic of Brugada syndrome, or type 2 (“saddle-back type”) pattern, which is only suggestive of Brugada syndrome. Variations in the ECG pattern can occur within a single patient and intermittently.
5. Pharmacological tests using a sodium-channel blocker drug should be used to evaluate suspected Brugada syndrome. Intravenous ajmaline and flecainide are the most widely used agents. The test is considered positive if a type 1 ECG pattern is identified during drug infusion.
6. Genetic testing is recommended only for the SCN5A gene (which encodes a cardiac sodium channel) where most (>500) pathogenic variations are located. Data support an autosomal dominant pattern. No genetic variant has been identified in 70% of affected families.
7. Diagnosis is established when a type 1 ST-segment elevation is observed either spontaneously or after intravenous administration of a sodium channel blocker in at least one right precordial lead (V1 or V2) placed in a standard or superior position.
8. For differential diagnosis, other causes of ST-segment elevation must be excluded:
   • Brugada ECG phenocopy may occur with right ventricle or right ventricular outflow tract pathology such as right ventricle ischemia, acute pulmonary embolism, or mechanical compression.
   • Brugada-like ECG patterns can occur with acute ischemia, left anterior descending artery occlusion, right bundle branch block, left ventricular hypertrophy, pectus excavatum, or arrhythmogenic cardiomyopathy.
9. Modulating factors such as bradycardia, vagal tone, fever (particularly in children), and certain medications can unmask or exacerbate Brugada syndrome.
10. Risk of SCD is higher in patients with syncope and spontaneous type 1 ECG pattern but intermediate in fever-induced type 1 ECG. An implantable cardioverter-defibrillator (ICD) may be considered in asymptomatic patients with inducible ventricular arrhythmias.
11. Treatment options include ICDs and medications, although ablation shows promise:
    • ICD is indicated in symptomatic patients.
    • Electrophysiology study may be performed in asymptomatic patients with spontaneous type 1 ECG.
    • Quinidine has a high rate of effectiveness (~80%) in the electrophysiology laboratory and has been used to suppress ventricular fibrillation in several clinical scenarios.
    • All patients should be educated regarding modulating or precipitating factors and taught to avoid these.

Clinical Topics: Arrhythmias and Clinical EP, Implantable Devices, EP Basic Science, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Novel Agents, Statins

Keywords: Brugada Syndrome, Death, Sudden, Cardiac, Electrocardiography, Arrhythmias, Cardiac, Syncope, Sodium Channel Blockers, Genetic Testing, Defibrillators, Implantable, Cardiac Electrophysiology, Quinidine

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